Naslov
Integrative epigenome-wide analysis demonstrates that DNA methylation may mediate genetic risk in inflammatory bowel disease

Autori
Ventham, N. T. ; Kennedy, N. A. ; Adams, A. T. ; Kalla, R. ; Heath, S. ; O'Leary, K. R. ; Drummond, H. ; IBD BIOM, consortium ; IBD CHARACTER, consortium ; Wilson, D. C. ; Gut, I. G. ; Nimmo, E. R. ; Satsangi, J.

Izvornik
Nature communications (2041-1723) 7 (2016); 13507, 14

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
inflammatory bowel disease ; DNA methylation ; epigenetics

Sažetak
Epigenetic alterations may provide important insights into gene-environment interaction in inflammatory bowel disease (IBD). Here we observe epigenome-wide DNA methylation differences in 240 newly-diagnosed IBD cases and 190 controls. These include 439 differentially methylated positions (DMPs) and 5 differentially methylated regions (DMRs), which we study in detail using whole genome bisulphite sequencing. We replicate the top DMP (RPS6KA2) and DMRs (VMP1, ITGB2 and TXK) in an independent cohort. Using paired genetic and epigenetic data, we delineate methylation quantitative trait loci ; VMP1/microRNA-21 methylation associates with two polymorphisms in linkage disequilibrium with a known IBD susceptibility variant. Separated cell data shows that IBD-associated hypermethylation within the TXK promoter region negatively correlates with gene expression in whole-blood and CD8+ T cells, but not other cell types. Thus, site-specific DNA methylation changes in IBD relate to underlying genotype and associate with cell-specific alteration in gene expression.

Izvorni jezik
Engleski

Znanstvena područja
Biologija

Napomena
Autori članovi IBD BIOM consortiuma
Lauc, Gordan ; Campbell, Harry ; McGovern, Dermot P.B. ; Annese, Vito ; Zoldoš, Vlatka ; Permberton, Iain K. ; Wuhrer, Manfred ; Kolarich, Daniel ; Fernandes, Daryl L. ; Theorodorou, Evropi ; Merrick, Victoria ; Spencer, Daniel I. ; Gardner, Richard A. ; Doran, Ray ; Shubhakar, Archana ; Boyapati, Ray ; Rudan, Igor ; Lionetti, Paolo ; Trbojević Akmačić, Irena ; Krištić, Jasminka ; Vučković, Frano ; Štambuk, Jerko ; Novokmet, Mislav ; Pučić-Baković, Maja ; Gornik, Olga ; Andriulli, Angelo ; Cantoro, Laura ; Sturniolo, Giancarlo ; Fiorino, Gionata ; Manetti, Natalia ; Latiano, Anna ; Kohn, Anna ; D’Incá, Renata ; Danese, Silvio ; Arnott, Ian D. ; Noble, Colin L. ; Lees, Charlie W. ; Shand, Alan G. ; Ho, Gwo-Tzer ; Dunlop, Malcolm G. ; Murphy, Lee ; Gibson, Jude ; Evenden, Louise ; Wrobe, Nicola l. ; Gilchrist, Tamara ; Fawkes, Angie ; Kammeijer, Guinevere S.M. ; Clerc, Florent ; de Haan, Noortje ; Vojta ; Aleksandar ; Samaržija, Ivana ; Markulin, Dora ; Klasić, Marija ; Dobrinić, Paula ; Aulchenko, Yurii ; van den Heuve, Tim ; Jonkers, Daisy ; Pierik, Marieke.

Autori članovi IBD CHARACTER consortiuma Vatn, Simen ; Ricanek, Petr ; Jahnsen, Jørgen ; You, Panpan ; Sølvernes, Janne ; Frengen, Anna B. ; Tannæs, Tone M. ; Moen, Aina E.F. ; Dahl, Fredrik A. ; Lindstrøm, Jonas Christoffer ; Ekeland, Gunn S. ; Detlie, Trond Espen ; Keita, Åsa V. ; Söderholm, Johan D. ; Henrik Hjortswang, Halfvarson, Jonas ; Bergemalm, Daniel ; Gomollón, Fernando ; D’Amato, Mauro ; Törkvist, Leif ; Hjelm, Fredrik ; Gullberg, Mats ; Nordberg, Niklas ; Ocklind, Anette ; Pettersson, Erik ; Ekman, Daniel ; Sundell, Mikael ; Modig, Eddie ; Veillard, Anne-Clémence ; Schoemans, Renaud ; Poncelet, Dominique ; Sabatel, Céline ; Gut, Marta ; Bayes, Monica ; Casén, Christina ; Lindahl, Torbjørn ; Ciemniejewska, Ewa ; Vatn, Morten H.

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